Application of Chromosomal Instability in Early Diagnosis of Biliary Tract Carcinoma

December 15, 2023 updated by: Fabiao zhang, Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University

Application of Chromosomal Instability and Metagenomic Detection in Early Diagnosis of Biliary Tract Carcinoma in Bile

Chromosomal instability (CIN) refers to ongoing chromosome segregation errors throughout consecutive cell divisions. CIN is a hallmark of human cancer, and it is associated with poor prognosis, metastasis, and therapeutic resistance. Analyzing CIN of the DNA extracted from cast-off cells in bile samples seems a promising method for diagnosing, monitoring, and predicting the prognosis of biliary tract carcinoma patients. CIN can be assessed using experimental techniques such as bulk DNA sequencing, fluorescence in situ hybridization (FISH), or conventional karyotyping. However, these techniques are either time-consuming or non-specific. The investigators here intend to study whether a new method named Bile Ultrasensitive Chromosomal Aneuploidy Detection (BileCAD), which is based on low-coverage whole-genome sequencing, can be used to analyze CIN and microbial infection analysis thus help diagnosing and treating biliary tract carcinoma patients.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Biliary tract carcinoma account for about 3% of all digestive system tumors, with potential high metastasis and invasion ability. Their early clinical symptoms lack specificity, and they are often found in late stage with poor prognosis. CIN results from errors in chromosome segregation during mitosis, leading to structural and numerical chromosomal abnormalities. It will generate genomic heterogeneity that acts as a substrate for natural selection. Furthermore, it is proved that tumors with aneuploidies and polyploidy resulting from whole-genome doubling are related with metastasis, treatment resistance, and decreased overall survival. It is estimated that 60%-80% of human tumors exhibit chromosomal abnormalities suggestive of CIN. CIN positively correlates with tumor stage and is enriched in relapsed as well as metastatic tumor specimens. Due to the ubiquity of CIN in cancer cells, it is a potentially way to detect CIN in the cast-off cells from the bile samples for diagnosing and monitoring biliary tract carcinoma patients. BileCAD is a new method to detecting CIN in the DNA sample from patients, including extracting DNA from bile, analyzing DNA by low-coverage whole-genome sequencing, processing the data by bio-information techniques, and finally optimizing the management of biliary tract carcinoma patients.The investigators intended to conduct a prospective study by analyzing bile samples from gallbladder cancers and cholangiocarcinoma patients and control groups that without any tumor in the Bile duct and gallbladder or other organs to compare the specificity and sensitivity of BileCAD test for diagnosing biliary tract carcinoma to other modalities, such as pathological diagnosis. At the same time, the consistency of BileCAD microbial analysis results and clinical microbial culture results was compared, so as to provide more reference for clinical diagnosis.

Study Type

Observational

Enrollment (Estimated)

300

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Zhejiang
      • Hangzhou, Zhejiang, China
        • Recruiting
        • Sir Run Run Shaw Hospital, School of Medicine，Zhejiang University
        • Contact:
      • Taizhou, Zhejiang, China
        • Recruiting
        • Taizhou Hospital of Zhejiang Province
        • Contact:
      • Taizhou, Zhejiang, China
        • Recruiting
        • Taizhou First People's Hospital
        • Contact:
      • Wenzhou, Zhejiang, China
        • Recruiting
        • First affiliated hospital of Wenzhou medical university
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Patients diagnosed with biliary tract carcinoma or participants in control group in Taizhou Hospital of Zhejiang Province, Taizhou First People's Hospital, The First Affiliated Hospital of Wenzhou Medical University and Sir Run Run Shaw Hospital from Apr 2023 until the end of this study.

Description

Inclusion Criteria:

  • No systemic therapy or biliary tract surgery before the trial.
  • Gallstones, bile duct space, obstructive jaundice and other suspected patients with biliary tract carcinoma.
  • Male or female patients aged >= 18 years.
  • Participants signed informed consent form.

Exclusion Criteria:

  • Age under 18 years.
  • Individuals unwilling to sign the consent form or unwilling to provide the medical record.
  • Individuals unwilling to participate in this trial.
  • Individuals has any active autoimmune disease or history of autoimmune disease.
  • Individuals have cardiac clinical symptoms or diseases that are not well controlled.
  • Individuals have uncontrolled severe cerebrovascular, pulmonary and other diseases.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Biliary tract carcinoma patients
Biliary tract carcinoma patients will be the experimental group to determine the sensitivity of BileCAD analysis.
Diagnostic test: The extracted DNA from bile samples will be analyzed by BileCAD to determine the level of CIN.
The extracted gDNA from bile sample will be analyzed by BileCAD to determine the level of CINs.
Non-cancer participants Patients
Non-cancer participants Patients being treated for other diseases but without any tumor will provide a negative control to provide data for determining the specificity of BileCAD analysis.
Diagnostic test: The extracted DNA from bile samples will be analyzed by BileCAD to determine the level of CIN.
The extracted gDNA from bile sample will be analyzed by BileCAD to determine the level of CINs.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Sensitivity of bile sample analysis by BileCADanalysis
Time Frame: 12 months
Number of patients "declared positive" with the BileCAD test among the patients suffered from biliary tract carcinoma.
12 months
Specificity of bile sample analysis by BileCADanalysis
Time Frame: 12 months
Number of patients "declared negative" with the BileCAD test among the patients without cancer.
12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
BileCAD microbial analysis results
Time Frame: 12 months
Consistency of BileCAD microbial analysis results with clinical microbial culture results
12 months
BileCAD analyzed the sensitivity of different types and locations of malignant tumors
Time Frame: 12 months
The tumors were classified into different types and sites and the sensitivity of BileCAD to different types and sites of malignant tumors was calculated.
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University

Collaborators

Sir Run Run Shaw Hospital
First Affiliated Hospital of Wenzhou Medical University
Taizhou First People's Hospital

Investigators

  • Principal Investigator: fabiao zhang, Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University
  • Principal Investigator: yunfeng shan, First affiliated hospital of Wenzhou medical university
  • Principal Investigator: ning mu, Taizhou First People's Hospital
  • Principal Investigator: xiao liang, Sir Run Run Shaw Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 30, 2023

Primary Completion (Estimated)

December 30, 2023

Study Completion (Estimated)

April 1, 2024

Study Registration Dates

First Submitted

April 25, 2023

First Submitted That Met QC Criteria

April 25, 2023

First Posted (Actual)

May 6, 2023

Study Record Updates

Last Update Posted (Estimated)

December 18, 2023

Last Update Submitted That Met QC Criteria

December 15, 2023

Last Verified

December 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BileCAD-330

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Biliary Tract Carcinoma

Clinical Trials on The extracted DNA from bile samples will be analyzed by BileCAD to determine the level of CIN.

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Hungary

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe